Publications by authors named "Roberto Biagini"

38 Publications

CT radiomics-based machine learning classification of atypical cartilaginous tumours and appendicular chondrosarcomas.

EBioMedicine 2021 Jun 26;68:103407. Epub 2021 May 26.

Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

Background: Clinical management ranges from surveillance or curettage to wide resection for atypical to higher-grade cartilaginous tumours, respectively. Our aim was to investigate the performance of computed tomography (CT) radiomics-based machine learning for classification of atypical cartilaginous tumours and higher-grade chondrosarcomas of long bones.

Methods: One-hundred-twenty patients with histology-proven lesions were retrospectively included. The training cohort consisted of 84 CT scans from centre 1 (n=55 G1 or atypical cartilaginous tumours; n=29 G2-G4 chondrosarcomas). The external test cohort consisted of the CT component of 36 positron emission tomography-CT scans from centre 2 (n=16 G1 or atypical cartilaginous tumours; n=20 G2-G4 chondrosarcomas). Bidimensional segmentation was performed on preoperative CT. Radiomic features were extracted. After dimensionality reduction and class balancing in centre 1, the performance of a machine-learning classifier (LogitBoost) was assessed on the training cohort using 10-fold cross-validation and on the external test cohort. In centre 2, its performance was compared with preoperative biopsy and an experienced radiologist using McNemar's test.

Findings: The classifier had 81% (AUC=0.89) and 75% (AUC=0.78) accuracy in identifying the lesions in the training and external test cohorts, respectively. Specifically, its accuracy in classifying atypical cartilaginous tumours and higher-grade chondrosarcomas was 84% and 78% in the training cohort, and 81% and 70% in the external test cohort, respectively. Preoperative biopsy had 64% (AUC=0.66) accuracy (p=0.29). The radiologist had 81% accuracy (p=0.75).

Interpretation: Machine learning showed good accuracy in classifying atypical and higher-grade cartilaginous tumours of long bones based on preoperative CT radiomic features.

Funding: ESSR Young Researchers Grant.
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http://dx.doi.org/10.1016/j.ebiom.2021.103407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170113PMC
June 2021

Outcome in dedifferentiated chondrosarcoma for patients treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study.

Eur J Cancer 2021 Jul 11;151:150-158. Epub 2021 May 11.

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy.

Introduction: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study.

Materials And Methods: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models.

Results: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles.

Conclusions: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
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http://dx.doi.org/10.1016/j.ejca.2021.04.017DOI Listing
July 2021

[F]FDG PET/CT quantitative parameters for the prediction of histological response to induction chemotherapy and clinical outcome in patients with localised bone and soft-tissue Ewing sarcoma.

Eur Radiol 2021 Mar 13. Epub 2021 Mar 13.

Nuclear Medicine Unit, IRCCS - Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144, Rome, Italy.

Objective: The application of [F]FDG PET/CT in predicting histologic response to induction chemotherapy in patients with Ewing sarcoma (EWS) has been proposed using the values of pre-post treatment SUV as a referral parameter, although with heterogeneous results. The aim of this retrospective study was to evaluate the diagnostic accuracy of [F]FDG PET/CT volumetric parameters (metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) as compared to SUV to predict response to chemotherapy and clinical outcome in patients with localised EWS of bone and soft-tissue.

Methods: Twenty-eight patients with non-metastatic EWS of bone (n = 20) and soft tissues (n = 8) who underwent a [F]FDG PET/CT scan before (PET) and after induction chemotherapy (PET) were enclosed in the analysis. Values of PET metrics (SUV, MTV, TLG) at diagnosis and after neoadjuvant chemotherapy as well as the percentage change between PET and PET (ΔSUV, ΔMTV and ΔTLG) were correlated to histological response and to progression-free survival (PFS).

Results: ΔTLG (cut-off: -60%) is the best predictor for histologic response with 100% sensitivity and 77.8% specificity. MTV > 33.4 cm and TLG > 112 were also associated with a favourable histologic response (sensitivity 80% and specificity 77.8% for both). On multivariate analysis, SUV (> 3.3) and ΔTLG (< -18%) were independent predictors of worse PFS.

Conclusions: [F]FDG PET/CT could accurately predict histologic response to neoadjuvant chemotherapy in patients with EWS, also showing a possible prognostic value for future disease relapse.

Key Points: • The variation of the PET parameter tumour lesion glycolysis (TLG) can predict the histologic response to induction chemotherapy (sensitivity 100%, specificity 77.8%), in patients with Ewing sarcoma. • The percentage variation of TLG and the value of the SUVmax at PET scan after chemotherapy show a prognostic role for future disease relapse. The combination of both the parameters identifies three prognostic classes of patients with low, intermediate and high risk of disease relapse.
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http://dx.doi.org/10.1007/s00330-021-07841-wDOI Listing
March 2021

Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration.

EMBO Mol Med 2021 Mar 15;13(3):e12778. Epub 2021 Feb 15.

Department of Biology, Rome University Tor Vergata, Rome, Italy.

The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions-pivotal aspects for cell survival and muscle contractile functionalities-together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.
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http://dx.doi.org/10.15252/emmm.202012778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933978PMC
March 2021

Antibacterial hydrogel coating in joint mega-prosthesis: results of a comparative series.

Eur J Orthop Surg Traumatol 2021 Feb 5. Epub 2021 Feb 5.

Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla, 3, 50134, Florence, Italy.

Purpose: Joint mega-prosthesis after bone tumors, severe trauma or infection is associated with high rates of post-surgical septic complications. A fast-resorbable antibacterial hydrogel coating (DAC®, Defensive Antibacterial Coating) has previously been shown to be able to significantly reduce surgical site infection in various clinical settings. Aim of the present study was to evaluate the safety and efficacy of the DAC hydrogel coating to prevent early periprosthetic joint infection after joint mega-prosthesis.

Methods: In this three-centers, case-control study, 43 patients, treated with an antibacterial hydrogel coated mega-prosthesis for oncological (N = 39) or non-oncological conditions (N = 4), were retrospectively compared with 43 matched controls, treated with mega-implants without the coating. Clinical, laboratory and radiographic examinations were performed to evaluate the occurrence of post-surgical infection, complications and adverse events.

Results: At a mean follow-up of 2 years, no evidence of infection or adverse events were observed in the DAC-treated group, compared to six cases of post-surgical infection in the control group.

Conclusion: This matched case-control study shows that a fast-resorbable, antibiotic-loaded coating can be safely used to protect joint mega-prosthesis, providing a reduction of early surgical site infections with no side effects. Larger prospective trials with longer follow-ups are warranted to confirm this report.

Trial Registration: RS1229/19 (Regina Elena National Cancer Institute Experimental Registry Number).
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http://dx.doi.org/10.1007/s00590-021-02884-7DOI Listing
February 2021

Symptoms and their implications on quality of life and psychological distress in sarcoma patients.

Future Oncol 2021 Mar 29;17(7):817-823. Epub 2021 Jan 29.

Psychology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

The aim of this study was to investigate symptoms, their variation over time and their relationship with quality of life (QoL)/psychological distress in sarcoma patients, as few data regarding QoL and psychological distress in this set of patients are currently available. A total of 188 sarcoma patients from an Italian referral center were involved. Symptoms and financial difficulties were evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire from the first treatment and over the follow-up period, up to 6 years. The authors found that patients with sarcoma experience several symptoms, especially fatigue and pain, which may dramatically worsen QoL and psychological distress. In conclusion, patients with sarcoma often experience fatigue, pain and financial difficulties, which negatively impacts QoL and psychological distress. To ameliorate overall QoL, proper control of symptoms is necessary.
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http://dx.doi.org/10.2217/fon-2020-0572DOI Listing
March 2021

The advantages of carbon fiber based orthopedic devices in patients who have to undergo radiotherapy.

Acta Biomed 2020 09 7;91(3):e2020057. Epub 2020 Sep 7.

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Background And Objectives: The modern approach to primary and secondary muscular skeletal tumors is multidisciplinary. The right combination of chemotherapy, surgery and radiotherapy (RT) makes obtaining local and distant disease control more likely. When surgery is indicated, radiotherapy often has a fundamental role as an adjuvant treatment; however, the titanium alloy instrumentations interfere with Radiotherapy setting, decreasing its effectiveness. It is common opinion that carbon fiber-reinforced devices are convenient in case of adjuvant RT in muscular skeletal oncology. The aim of the study is to support this intuition with experimental data, verifying the more accurate estimation of the delivered dose during RT, comparing Carbon Fiber-Reinforced PEEK (CFRP) plates with titanium-alloy orthopedic devices in order to evaluate their effects on target volume identification and dose distribution for radiation treatment.

Methods: Phantoms were then irradiated with a linear accelerator Varian 2100 C/D with photon beams of 6 and 15 MV energies. Absorbed dose in the point of interest was verified by EBT3 gafchromic films above and below the two materials. Images from CT simulations were also analyzed in terms of Hounsfield numbers in patients with titanium and carbon fiber orthopedic implants in the spine or in the femur.

Results: For a 6 MV photon beam, the doses measured just under the titanium-alloy plate were less than approximately 20% of the value calculated by the TPS. For a 15 MV beam energy, these differences were slightly lower. Using CFRP plate, the difference between measured and calculated doses was within ±3% for both energies, which was comparable with the statistical uncertainties. In the cases of simulated treatment of humerus titanium implants, the difference varies in range ± 10% with hot spot of + 10% and cold spot of -15%.

Conclusions: The use of CFRP for orthopedic devices and implants provides a valuable advantage in identifying the target due to the reduction of artifacts. Clear imaging of the soft tissues surrounding the bone is useful and reduces the discrepancies between calculated/delivered and measured doses, generating a more homogeneous dose distribution. Furthermore, there is a significant benefit in detecting the state of disease in CT imaging during the follow-up of treated patients. In-vivo studies are encouraged to verify whether a more effective radiotherapy leads to a decrease in local recurrence and local progression.
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http://dx.doi.org/10.23750/abm.v91i3.7769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716998PMC
September 2020

Diagnostic and Clinical Impact of 18F-FDG PET/CT in Staging and Restaging Soft-Tissue Sarcomas of the Extremities and Trunk: Mono-Institutional Retrospective Study of a Sarcoma Referral Center.

J Clin Med 2020 Aug 6;9(8). Epub 2020 Aug 6.

Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.

Background: Soft-tissue sarcomas (STS) represent a wide heterogeneous class of rare tumors. The exact role F-fluorodeoxyglucose positron emission/computed tomography (F-FDG PET/CT) in the evaluation of STS is not well established. The aim of the present study was to evaluate how the use of F-FDG PET/CT in STS could influence patient therapy planning, looking for a possible added value over computed tomography and magnetic resonance imaging-the most used modalities in the study of STS. Differences in SUV according to histologic subtype and tumor grade were also considered.

Methods: a total of 345 consecutive F-FDG PET/CT scans performed for initial staging ( = 171) or for suspected disease relapse ( = 174) in 282 patients with STS extracted from the local Information System database were retrospectively reviewed.

Results: F-FDG PET/CT altered therapy planning in 80 cases (16.4% for staging and 29.9% in restaging), both for disease upstaging (58.8%) and downstaging (41.2%) Conclusions: F-FDG PET/CT could significantly influence management of patients with STS, particularly for restaging.
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http://dx.doi.org/10.3390/jcm9082549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463806PMC
August 2020

The Real-Life Journey of Elderly Patients in Soft Tissue and Bone Sarcomas: A Retrospective Analysis from a Sarcoma Referral Center.

J Clin Med 2020 Aug 4;9(8). Epub 2020 Aug 4.

Oncological Orthopaedics Unit, IRCCS-Regina Elena National Cancer Institute, 00161 Rome, Italy.

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue (STS) and bone sarcomas (BS) followed by our Sarcoma Disease Management Team from 2012 to 2017. One-hundred and twenty-three patients with a median age of 77 years (range: 70-92) were identified. STS were the most common histological subtypes (94%) and the grade was high in 79/123 patients (64%). At diagnosis, 88% of patients had localized disease (LD) and 12% were metastatic (MD). Overall, 96% of patients with LD underwent surgery, 46/54 (85%) with high grade STS patients underwent complementary radiotherapy, and 10/54 (19%) received adjuvant treatments. Twelve out of 33 patients who relapsed (36%) underwent local therapies. Seventeen (52%) and eight (24%) patients were treated with first-line and second-line medical treatments, respectively. Tolerability to systemic treatments was fairly good. Overall, 21% of the patients with advanced disease were candidates for best supportive care alone. Our case series of elderly patients with both STS and BS shows that personalized multidisciplinary treatment can nevertheless be offered to this frail population in order to control the evolution of disease.
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http://dx.doi.org/10.3390/jcm9082503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465593PMC
August 2020

Reorganization Tips from a Sarcoma Unit at Time of the COVID-19 Pandemic in Italy: Early Experience from a Regional Referral Oncologic Center.

J Clin Med 2020 Jun 15;9(6). Epub 2020 Jun 15.

Department of Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.

Since the World Health Organization declared the novel coronavirus outbreak a global health emergency, Italy's lockdown was declared on 9 March 2020. Elective orthopedic surgery was forced to stop to allow the healthcare system to face the emergency. However, many orthopedic oncology cases could not be postponed. The aim of this study was to report the experience in managing sarcoma patients and the reorganization of a cancer center in an attempt to maintain it free from COVID-19. A Coronavirus Crisis Unit was established by the health directorate coordination in order to adopt specific procedures. General rules of screening and social distancing were applied in different health settings (entrance check point, hospital inward, outpatient clinic, operative room). Regarding oncologic orthopedics, priority was given to bone and soft tissue sarcomas, metastases and aggressive benign tumors at risk of impending or pathologic fracture. Precise indications were followed to manage first outpatient visits, patients undergoing surgery and follow-up. Meticulous adherence to rules among patients and personnel and collaboration between leadership and medical staff in order to continue to perform multidisciplinary treatment protocols, maintain the availability of infrastructural spaces and source protective equipment, swabs and screening samples have been successful in the aim towards a safe cure for cancer patients.
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http://dx.doi.org/10.3390/jcm9061868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357067PMC
June 2020

Sarcoma patients' quality of life from diagnosis to yearly follow-up: experience from an Italian tertiary care center.

Future Oncol 2019 Sep 12;15(27):3125-3134. Epub 2019 Sep 12.

Psychology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

To investigate sarcoma patients' perception of quality of life and psychosocial distress across the different disease's stages.  Total 329 sarcoma patients were monitored from diagnosis up to a maximum of six consecutive follow-up visits. Functional status worsened over time with the lowest value after surgery and a full recovery not earlier than the second follow-up visit. Married and single patients exhibited similar quality of life pattern. High levels of psychological distress were observed from diagnosis to active treatment periods with a progressive improvement during follow-up. Psychological distress pattern over time varied by marital status and age. Our study suggests the importance of integrating psychosocial care to medical therapy across the entire sarcoma journey.
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http://dx.doi.org/10.2217/fon-2019-0237DOI Listing
September 2019

F-FDG PET/CT in the evaluation of cartilaginous bone neoplasms: the added value of tumor grading.

Ann Nucl Med 2019 Nov 8;33(11):813-821. Epub 2019 Aug 8.

Oncological Orthopaedics Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.

Objectives: Cartilaginous bone tumors represent a wide variety of neoplasms ranging from benign to extremely aggressive malignant lesions. Unlike other tumors, the biopsy cannot easily predict the histological grade, sometimes not allowing choosing the best therapeutic approach. The aim of the study was to evaluate the ability of F-FDG PET/CT to differentiate enchondroma from chondrosarcoma and to predict the histological grade as compared to biopsy.

Methods: F-FDG PET/CT of 95 patients with chondroid lesions were retrospectively evaluated. The best SUV cutoff to predict the post-surgical histological grade were correlated to those of biopsy and to several radiologic aggressiveness features, which were summarized in the parameter "Radiologic Aggressiveness Score" (AgSCORE).

Results: A concordance between the preoperative biopsy and the definitive histological grade was observed overall in 78.3% of patients, the lowest accuracy (58.6%) being in the identification of intermediate/high-grade chondrosarcoma (G2/G3). The best SUV cutoff was 2.6 to discriminate enchondroma vs. low-grade chondrosarcoma (sensitivity 0.68, specificity 0.86), 3.7 to differentiate low-grade vs. intermediate/high-grade chondrosarcoma (sensitivity 0.83, specificity 0.84) and 7.7 to differentiate intermediate/high-grade vs. dedifferentiated chondrosarcoma (sensitivity 0.92, specificity 0.9). The AgSCORE also showed a high accuracy to differentiate between G1 and G2/G3 chondrosarcoma (cutoff = 4; sensitivity 0.76; specificity 0.89). An even higher accuracy was observed in those cases in which both SUV and AgSCORE cutoff were concordant.

Conclusions: Results in this large series of patients suggest a potential role of F-FDG PET/CT for histological grading of cartilaginous tumors, thus helping the orthopedic surgeon towards the most appropriate surgical procedure.
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http://dx.doi.org/10.1007/s12149-019-01392-3DOI Listing
November 2019

Percutaneous management of bone metastases: state of the art, interventional strategies and joint position statement of the Italian College of MSK Radiology (ICoMSKR) and the Italian College of Interventional Radiology (ICIR).

Radiol Med 2019 Jan 6;124(1):34-49. Epub 2018 Sep 6.

Department of Biotechnological and Applied Clinical Sciences, Division of Radiology Oncology, University of L'Aquila, L'Aquila, Italy.

Interventional radiology provides local management of bone metastases (BM) with a palliative intent in most cases, or with a curative intent in selected patients. Its role has rapidly expanded in the last decade, offering new treatment solutions often in combination with surgery, radiation therapy and medical treatments. The aim of the present paper is to increase awareness, acceptance and adoption of interventional radiology procedures for the treatment of BM; and to present the joint position of the Italian College of Musculoskeletal Radiology and the Italian College of Interventional Radiology.
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http://dx.doi.org/10.1007/s11547-018-0938-8DOI Listing
January 2019

HMGA1/E2F1 axis and NFkB pathways regulate LPS progression and trabectedin resistance.

Oncogene 2018 11 6;37(45):5926-5938. Epub 2018 Jul 6.

Cellular Network and Molecular Therapeutic Target Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Roma, Italy.

Although the medical treatments of sarcoma have evolved in the last years, a significant portion of patients develops recurrence after therapies suggesting the need to identify novel targets to improve the treatments. By the use of patient-derived and established cell lines from liposarcoma, as well as specimens from patient biopsies, we found that HMGA1 is involved in the progression of dedifferentiated and myxoid liposarcoma. The immunohistochemical and RT-PCR analyses of 68 liposarcoma specimens revealed a significant high expression of HMGA1, at the protein and RNA levels, both in myxoid and dedifferentiated liposarcoma subtypes compared with differentiated ones. Loss- and gain-of-function experiments by HMGA1-specific depletion and overexpression in dedifferentiated and myxoid liposarcoma cells showed the contribution of this oncogenic factor in cell proliferation, motility, invasion, and drug resistance. The in vitro and in vivo treatment of myxoid liposarcoma with trabectedin, a drug with a potent anti-tumor activity, revealed downregulation of HMGA1, E2F1, and its-downstream targets, vimentin and ZEB1, indicating a critical role of trabectedin in inhibiting the mesenchymal markers of these tumors through the HMGA1/E2F1 axis. These data were also confirmed in patients' tumor biopsies being HMGA1, E2F1, and vimentin expression significantly reduced upon trabectedin therapy, administered as neo-adjuvant chemotherapy. Furthermore, trabectedin treatment inhibits in vitro NFkB pathway in mixoyd liposarcoma sensitive but not in resistant counterparts, and the inhibition of NFkB pathway re-sensitizes the resistant cells to trabectedin treatment. These data support the rational for combining NFkB inhibitors with trabectedin in liposarcoma patients, who have become resistant to the drug.
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http://dx.doi.org/10.1038/s41388-018-0394-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224401PMC
November 2018

Precision diagnostics of Ewing's sarcoma by liquid biopsy: circulating fusion transcripts.

Ther Adv Med Oncol 2018 1;10:1758835918774337. Epub 2018 Jun 1.

Oncogenomics and Epigenetics, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Background: Limited information is available on the applicative value of liquid biopsy (LB) in rare tumors, including Ewing's sarcoma (ES). The accepted precision diagnostics standards would greatly benefit from a non-invasive LB test monitoring pathognomonic gene rearrangements in the bloodstream.

Methods: Tissue and blood samples were collected from six and four ES patients, respectively. Plasma was cleared by two successive rounds of centrifugation and stored frozen until RNA extraction by the QIAmp CNA kit. RNA was retro-transcribed and subjected to real-time quantitative polymerase chain reaction (RT-qPCR) and digital polymerase chain reaction (dPCR). Reactions were set up using two custom primer sets identifying types 1 and 2 fusion transcripts.

Results: The two prevalent types of rearrangements could be identified using only two sets of polymerase chain reaction primers, regardless of patient-specific DNA breakpoints. RT-qPCR and dPCR discriminated the two variants in five tumor tissue RNAs and in four circulating tumor RNAs (ctRNAs). Of note, molecular diagnosis was possible using blood samples even when tumor tissue was not available. ctRNA levels correlated ( < 0.05) with volume-based positron emission tomography (PET) parameters (metabolic tumor volume and total lesion glycolysis), and allowed the fine tracking of disease course after surgery, during adjuvant as well as neoadjuvant chemotherapy, and at follow up in one patient.

Conclusions: To our knowledge, this is one of the few single-marker LB assays in solid tumors specifically designed to detect rearranged RNAs in blood, and the first study describing circulating tumor RNAs in ES patients. Altogether, our results support the idea that LB may have a considerable impact on ES patient monitoring and management.
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http://dx.doi.org/10.1177/1758835918774337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985603PMC
June 2018

Anterior robotic approach in en-bloc sacrectomy: a preliminary experience.

J Robot Surg 2019 Feb 27;13(1):53-59. Epub 2018 Mar 27.

Orthopedic Oncology Unit, Department of Experimental Clinical Oncology, "Regina Elena" National Cancer Institute, Rome, Italy.

En-bloc sacrectomy is a highly demanding surgical procedure necessary to obtain wide margin in sacral tumor. The double approach, anterior and posterior approach, is usually preferred for tumors extending proximally to S3 level where iliac internal vessels are at a higher risk for damage during posterior surgery. It can be justified also in selected cases to decrease the risk of posterior approach as in local recurrence or in patients who already underwent laparotomy. Our intent was to apply robotic-assisted techniques for performing anterior preparatory approach for sacrectomy surgery. Between December 2010 and December 2014, three cases of sacrectomies were performed in a previous robotic-assisted preparatory approach to separate the rectum from the tumor. Dissections were successfully performed in all cases close to the pelvic floor. The surgeon was able to position a Gore-Tex spacer between the anterior tumor surface and the rectum in all cases. The anterior dissections were performed with a perfect control of bleeding. No complications related to the anterior approach were reported. Robot-assisted surgery can be considered a valid and minimally invasive technique which allows a safe anterior dissection of the pelvic structures dividing tumors from surrounding tissues. It allows to place a spacer to protect organs during posterior sacral resection performed on the same day or at a later time. Further experiences are advocated to evaluate its efficiency in sacral tumors of greater size.
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http://dx.doi.org/10.1007/s11701-018-0807-4DOI Listing
February 2019

Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin cytotoxicity in preclinical models of human sarcoma.

Oncogenesis 2018 Feb 23;7(2):20. Epub 2018 Feb 23.

Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Sarcomas are rare tumors with generally poor prognosis, for which current therapies have shown limited efficacy. Histone deacetylase inhibitors (HDACi) are emerging anti-tumor agents; however, little is known about their effect in sarcomas. By using established and patient-derived sarcoma cells with different subtypes, we showed that the pan-HDACi, ITF2357, potently inhibited in vitro survival in a p53-independent manner. ITF2357-mediated cell death implied the activation of mitochondrial apoptosis, as attested by induction of pro-apoptotic BH3-only proteins and a caspases-dependent mechanism. ITF2357 also induced autophagy, which protected sarcoma cells from apoptotic cell death. ITF2357 activated forkhead box (FOXO) 1 and 3a transcription factors and their downstream target genes, however, silencing of both FOXO1 and 3a did not protect sarcoma cells against ITF2357-induced apoptosis and upregulated FOXO4 and 6. Notably, ITF2357 synergized with Doxorubicin to induce cell death of established and patient-derived sarcoma cells. Furthermore, combination treatment strongly impaired xenograft tumor growth in vivo, when compared to single treatments, suggesting that combination of ITF2357 with Doxorubicin has the potential to enhance sensitization in different preclinical models of sarcoma. Overall, our study highlights the therapeutic potential of ITF2357, alone or in rational combination therapies, for bone and soft tissue sarcomas management.
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http://dx.doi.org/10.1038/s41389-018-0026-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833676PMC
February 2018

Carbon-fiber reinforced intramedullary nailing in musculoskeletal tumor surgery: a national multicentric experience of the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.

Injury 2017 Oct;48 Suppl 3:S55-S59

The Italian Orthopaedic Society (SIOT), Rome, Italy.

Introduction: Carbon fiber reinforced (CFR) implants have been proposed for the treatment of fractures or impending fractures of the long bones in the oncology patient. Aim of this study is to present the largest cohort of oncology patients operated by CFR nailing by the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.

Methods: 53 adult oncology patients were operated on with a CFR-PEEK nail. All the data from adjuvants therapies were collected. Bone callus formation, response to radiotherapy, relapse or progression of the osteolysis were recorded. Hardware survival and failure, breakage and need for implant revision were also analysed.

Results: Anatomical implantation of nails include humerus (n = 35), femur (n =11) and tibia (n = 7). The most frequent tumors affecting the bone were myeloma (n = 13), breast (n = 11), lung (n = 8), and renal cell cancer (n = 7). Acrylic cement reinforcement was used in 2 patients. One patient was subjected to electrochemotherapy after nail insertion. Intraoperative and early postoperative complications occurred in 13.2% and 7.54% of patients respectively. Eight patients had local progression and one developed a stress fracture proximally to the distal static screw. Radiographic union occurred in 14 patients; one screw loosening was recorded.

Discussion: There is currently a lack of solid evidence on the clinical use of CFR nails in oncologic patients. This is the first and largest study of CFR nailing, with the longest available follow up.

Conclusions: Implant related complications and surgery-related morbidity should be taken into account in the decision-making process for the surgical management of these patients. These data can improve the surgeon-patient communication and guide further studies on patients' survival and complications with respect to surgery.
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http://dx.doi.org/10.1016/S0020-1383(17)30659-9DOI Listing
October 2017

The dual mobility cup in muscular skeletal oncology: rationale and indications.

Int Orthop 2017 Mar 31;41(3):447-453. Epub 2017 Jan 31.

Oncological Orthopedics Department, IFO - Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy.

Purpose: Because of the improvement of medical therapy and the corresponding increase in life expectancy, orthopaedic surgeons are obliged to perform more wide resections rather than intramedullary stabilization nailing for patients affected by tumours of the hip compared to the past. Wide resection often causes joint instability, so prosthetic reconstruction presents a higher risk of dislocation than in primary osteoarthritis cases. The aim of the present paper is to classify the indications for the dual mobility cup (DMC) hip prosthesis based on the anatomic structures involved in the disease and to analyse the rationale to reduce the risk of dislocation.

Methods: Indications were analyzed and classified based on all the cases in which the DMC prosthesis was used for reconstruction after hip resection in an oncological research hospital.

Results: Four classes of indications were identified; for classes I and IV the indication for DMC prosthesis can be considered strong; for classes II and III the indications must be evaluated considering the specific case, based on life expectancy, performance status, presence of osteoarthritis, and availability of adjuvant local therapies. When the DMC prosthesis is indicated, the cup should always be cemented, either alone or with augmentation techniques, to decrease the risk of mobilization due to local disease progression.

Conclusions: DMC can be a valid alternative in reconstruction of the hip after tumor removal; nevertheless, prospective, randomized studies are necessary to verify the real dislocation rate based on the entity of resection.
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http://dx.doi.org/10.1007/s00264-017-3407-4DOI Listing
March 2017

Reconstruction after musculoskeletal sarcomas: how to avoid a surgical trap.

Minerva Chir 2017 Apr 16;72(2):108-120. Epub 2016 Dec 16.

Department of Plastic and Reconstructive Surgery, IFO - Regina Elena National Cancer Institute, Rome, Italy.

Background: Musculoskeletal sarcomas comprise 1% of all malignancies in adults. Unfortunately, sometimes they are addressed in non-appropriate way requiring a more invasive procedure to achieve radical surgery at a later date. Due to incomplete predictability of their extension, scheduled reconstruction cannot be performed at times, forcing plans to change or clogging up immediate reconstruction. In this paper, the authors provide an insight in the treatment of musculoskeletal sarcomas, particularly focusing on the preoperative planning of reconstructive strategies, which is crucial in order to prevent unpleasant surprises during reconstruction.

Methods: Fifty-six consecutive patients requiring reconstructive procedures following the extirpation of tumors were recruited. All data collected during the diagnostic phase were analyzed collectively during a multi-disciplinary meeting where the surgical procedure was planned. A score system was created and results were then classified into "excellent", "good", "sufficient" and "poor".

Results: After a minimum follow up of 12 months, we recorded the following results: excellent in 10 patients (17.9%), good in 28 patients (50%), sufficient in 12 cases (21.4%) and poor in 6 cases (10.7%).

Conclusions: The improvement of treatment and the long-lasting survival in musculoskeletal sarcoma have shifted the goal of therapeutic protocol to obtaining radical tumor removal and maximum functional restoration. When facing unpredictable extension of the resections, reconstruction may be a challenging or even impossible task to fulfil. Only meticulous preoperative planning can prevent surgeons from falling into all sorts of surgical traps following wide resections.
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http://dx.doi.org/10.23736/S0026-4733.16.07185-6DOI Listing
April 2017

Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model.

Int J Mol Sci 2016 Aug 22;17(8). Epub 2016 Aug 22.

Department of Molecular Cell Biology, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE Leiden, The Netherlands.

Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient's medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.
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http://dx.doi.org/10.3390/ijms17081375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000770PMC
August 2016

The Carbofix™ "Piccolo Proximal femur nail": A new perspective for treating proximal femur lesion. A technique report.

J Orthop 2016 Dec 6;13(4):343-6. Epub 2016 Jul 6.

Oncological Orthopedics, IFO - Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy.

Metastases to proximal femur are common and surgery is often suggested to prevent fractures; otherwise it is necessary in cases where this has already occurred. Adjuvant radiotherapy is necessary to reduce the risk of local progression. Nevertheless, the success or failure of radiation therapy treatments depends upon the accuracy in which target identification is correct and dose prescription is fulfilled. Unfortunately, the use of titanium nails consistently limits radiation dose; indeed, the presence of ferromagnetic artifacts interferes with target identification. We present the technique for implant a new carbon fiber nail useful to reduce the ferromagnetic artifacts which allows a better adjuvant radiotherapy.
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http://dx.doi.org/10.1016/j.jor.2016.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939471PMC
December 2016

miR-181c associates with tumor relapse of high grade osteosarcoma.

Oncotarget 2015 Jun;6(16):13946-61

Molecular Chemoprevention Unit, Regina Elena National Cancer Institute, Rome, Italy.

High-grade osteosarcoma (OS) is characterized by low incidence, high aggressiveness and moderate 5-years survival rate after aggressive poly-chemotherapy and surgery. Here we used miRNA profiling as a tool to possibly predict and monitor OS's development and therapeutic outcome. First, we evaluated the altered expression of selected miRNAs from a case of Giant Cell Tumor (GCT) apparently evolved into an OS. We found that most of modulated miRs were associated with pathways of bone resorption and osteogenesis. miRNA expression also revealed that GCT and OS were distinct tumors. Second, we validated the observed miRNA profile in two independent casuistries of ten GCT (not evolved into malignant tumors) and sixteen OS patients. Interestingly, we found that miR-181c and other three miRNAs identified in the first step of the study were also consistently de-regulated in all OS patients. Ectopic expression of miR-181c reduced cell viability and enhanced chemotherapeutic-induced cell death of U2OS and SAOS2 cells. These findings indicate that: i) miRNAs aberrantly modulated in GCT could be predictive of its development into OS and ii) miRNAs expression could be useful to monitor the OS therapeutic outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546443PMC
http://dx.doi.org/10.18632/oncotarget.3539DOI Listing
June 2015

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations.

BMC Cancer 2015 May 22;15:424. Epub 2015 May 22.

The Italian Orthopaedic Society Bone Metastasis Study Group, Via Nicola Martelli, 3, 00197, Rome, Italy.

Background: We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data.

Methods: We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia).

Results: The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery.

Conclusions: PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied.
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http://dx.doi.org/10.1186/s12885-015-1396-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443666PMC
May 2015

Bone metastases of unknown origin: epidemiology and principles of management.

J Orthop Traumatol 2015 Jun 1;16(2):81-6. Epub 2015 Mar 1.

Oncologic Center, "Palazzo Baleani", Teaching Hospital Policlinico Umberto I, Rome, Italy.

Unlabelled: Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin-eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4-8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt to provide the most appropriate therapy for the primary tumor as soon as possible.

Level Of Evidence: 5.
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http://dx.doi.org/10.1007/s10195-015-0344-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441638PMC
June 2015

Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

Tumori 2014 Nov-Dec;100(6):612-9

Background: Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study).

Patients And Methods: Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity.

Results: From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively.

Conclusions: This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.
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http://dx.doi.org/10.1700/1778.19262DOI Listing
May 2015

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.

Lancet Oncol 2015 Jan 11;16(1):98-107. Epub 2014 Dec 11.

Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy; Department of Oncology, University of Torino, Turin, Italy.

Background: Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment.

Methods: We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01804374.

Findings: We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28-61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths.

Interpretation: Although the combination of sorafenib and everolimus showed activity as a further-line treatment for patients with advanced or unresectable osteosarcoma, it did not attain the prespecified target of 6 month PFS of 50% or greater.

Funding: Italian Sarcoma Group.
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http://dx.doi.org/10.1016/S1470-2045(14)71136-2DOI Listing
January 2015

Giant cell tumor of the mobile spine: a review of 49 cases.

Spine (Phila Pa 1976) 2012 Jan;37(1):E37-45

Department of Spine Oncology, Rizzoli Institute, Bologna, Italy.

Study Design: This is a retrospective review of 49 cases of giant cell tumor (GCT) of the mobile spine treated surgically.

Objective: Our goal was to determine which factors influenced local recurrence.

Summary Of Background Data: GCT is a benign, locally aggressive tumor that rarely occurs in the spine. The management of local recurrence can be challenging.

Methods: We performed a retrospective analysis of GCTs of the mobile spine managed between 1970 and 2005. Median follow-up was 145 months with a minimum of 2 years or until death. We used the Kaplan-Meier method to test whether Enneking stage, surgery type, and surgical margin had statistically significant impact on local recurrence. The log rank test was used for comparison, and a P value of less than 0.05 was deemed significant.

Results: Of the 49 patients, 11 (22%) local recurrences occurred. The latest recurrence occurred at 60 months. Age less than 25 years was associated with a worse relapse-free survival (P = 0.03). En bloc resection was associated with better local control with Enneking stage III tumors (P = 0.01); however, intralesional resection provided adequate control of Enneking stage II tumors. There were 6 (12%) cases of metastasis, and 2 patients died from the progression of their disease. One patient died from the complications of the surgery.

Conclusion: En bloc resection should be considered for Enneking stage III GCTs of the mobile spine. The choice of en bloc resection must be balanced with the inherent risks of the procedure. Intralesional resection of Enneking stage II tumors provides adequate local control. Patients should be followed for at least 5 years because local relapse can occur late.
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http://dx.doi.org/10.1097/BRS.0b013e3182233ccdDOI Listing
January 2012

Spinal instability neoplastic score: an analysis of reliability and validity from the spine oncology study group.

J Clin Oncol 2011 Aug 27;29(22):3072-7. Epub 2011 Jun 27.

University of Saskatchewan, Royal University Hospital, 103 Hospital Dr, Saskatoon, Saskatchewan, Canada.

Purpose: Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS).

Methods: Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group. The median category for each patient case (consensus opinion) was used as the gold standard for predictive validity testing. On two occasions at least 6 weeks apart, each rater also scored each patient using SINS. Each total score was converted into a three-category data field, with 0 to 6 as stable, 7 to 12 as potentially unstable, and 13 to 18 as unstable.

Results: The κ statistics for interobserver reliability were 0.790, 0.841, 0.244, 0.456, 0.462, and 0.492 for the fields of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively. The κ statistics for intraobserver reliability were 0.806, 0.859, 0.528, 0.614, 0.590, and 0.662 for the same respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were 0.846 (95% CI, 0.773 to 0.911) and 0.886 (95% CI, 0.868 to 0.902), respectively. The κ statistic for predictive validity was 0.712 (95% CI, 0.676 to 0.766).

Conclusion: SINS demonstrated near-perfect inter- and intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively.
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http://dx.doi.org/10.1200/JCO.2010.34.3897DOI Listing
August 2011

A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group.

Spine (Phila Pa 1976) 2010 Oct;35(22):E1221-9

Combined Neurosurgery and Orthopaedic Spine Program, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.

Study Design: Systematic review and modified Delphi technique.

Objective: To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability.

Summary Of Background Data: Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors.

Methods: We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability.

Results: A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus.

Conclusion: The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor.
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http://dx.doi.org/10.1097/BRS.0b013e3181e16ae2DOI Listing
October 2010
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